Effect of antagonists of platelet-activating factor receptors on memory of inhibitory avoidance in rats

Diana Jerusalinsky, Cyntia Fin, Jorge A. Quillfeldt, Maria Beatriz C. Ferreira, Paulo K. Schmitz, Ricardo C. Da Silva, Roger Walz, Nicolas G. Bazan, Jorge H. Medina, Ivan Izquierdo
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引用次数: 22

Abstract

Platelet-activating factor (PAF) is present in the brain.It enhances glutamate release and long-term potentiation (LTP) through an action on synaptic membrane receptors sensitive to the antagonist, BN 52021, and has been proposed as a retrograde messenger in the genesis of LTP. In addition, PAF has other, metabolic actions mediated by microsomal receptors sensitive to the antagonist, BN 50730. We investigated the effect on memory of the preor post-training infusion of BN 52021 or BN 50730 into the hippocampus and that of BN 52021 in the amygdala and the entorhinal cortex. Male Wistar rats were implanted bilaterally with cannulae aimed at these brain regions. After recovery from surgery, the animals were trained in step-down inhibitory avoidance using a 0.5-mA foot shock and tested for retention 24 h later. BN 52021 (0.5 μg/side) was amnestic when given into the hippocampus or the amygdala either before or immediately after training but not 30 or 100 min later. BN 52021 was also amnestic when given into the entorhinal cortex 100 but not 0 or 300 min after training. Intrahippocampally administered BN 50730 had no effect on memory. The findings are compatible with the suggestion from previous findings that memory of this task depends on the generation of LTP at the time of training in hippocampus and amygdala and, 90–180 min later, in the entorhinal cortex.

血小板活化因子受体拮抗剂对大鼠抑制性回避记忆的影响
血小板活化因子(PAF)存在于大脑。它通过作用于对拮抗剂BN 52021敏感的突触膜受体来增强谷氨酸释放和长期增强(LTP),并被认为是LTP发生中的逆行信使。此外,PAF还有其他代谢作用,由对拮抗剂bn50730敏感的微粒体受体介导。我们研究了训练前后海马中注入BN 52021或BN 50730以及杏仁核和内嗅皮层中注入BN 52021对记忆的影响。在雄性Wistar大鼠的双侧植入针对这些脑区的套管。手术恢复后,使用0.5 ma足部电击训练动物进行降压抑制性回避训练,并在24小时后测试保留率。BN 52021 (0.5 μg/侧)在训练前或训练后立即给予海马或杏仁核,而在训练后30或100分钟不给予。BN 52021在训练后100分钟,而不是0分钟或300分钟注射到内嗅皮层时也会失忆。海马内给药BN 50730对记忆没有影响。这一发现与之前的研究结果一致,即该任务的记忆取决于训练时海马和杏仁核以及90-180分钟后内嗅皮层LTP的产生。
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